Genetic Variant SALL1:p.Ser88Arg (chr16-51141958-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002968.3(SALL1):c.264C>A(p.Ser88Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S88S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SALL1
NM_002968.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0230

Publications

1 publications found

Variant links:

Genes affected

SALL1 (HGNC:10524): (spalt like transcription factor 1) The protein encoded by this gene is a zinc finger transcriptional repressor and may be part of the NuRD histone deacetylase complex (HDAC). Defects in this gene are a cause of Townes-Brocks syndrome (TBS) as well as bronchio-oto-renal syndrome (BOR). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SALL1 Gene-Disease associations (from GenCC):

Townes-Brocks syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
Townes-Brocks syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SALL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.055216104).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002968.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL1	NM_002968.3	MANE Select	c.264C>A	p.Ser88Arg	missense	Exon 2 of 3	NP_002959.2
	SALL1	NM_001127892.2		c.-28C>A		5_prime_UTR	Exon 2 of 3	NP_001121364.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SALL1	ENST00000251020.9	TSL:1 MANE Select	c.264C>A	p.Ser88Arg	missense	Exon 2 of 3	ENSP00000251020.4
SALL1	ENST00000566102.1	TSL:1	c.77-4406C>A		intron	N/A	ENSP00000455582.1
SALL1	ENST00000440970.6	TSL:5	c.264C>A	p.Ser88Arg	missense	Exon 3 of 4	ENSP00000407914.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000797

AC:

AN:

251042

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461678

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5658

European-Non Finnish (NFE)

AF:

0.00000719

AC:

AN:

1111944

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.0

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.31

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.77

M_CAP

Benign

0.0081

MetaRNN

Benign

0.055

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.95

PhyloP100

0.023

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.3

REVEL

Benign

0.069

Sift

Benign

0.43

Sift4G

Benign

0.45

Polyphen

0.0

Vest4

0.15

MutPred

0.19

Loss of glycosylation at S88 (P = 0.0013)

MVP

0.13

MPC

0.23

ClinPred

0.026

GERP RS

-0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.057

gMVP

0.10

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over