rs753870808

Variant names:

• chr15-78880527-A-G
• rs753870808
• NM_006791.4:c.103A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-78880527-A-G
• chr15-78880527-A-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006791.4(MORF4L1):​c.103A>G​(p.Ile35Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000759 in 1,450,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: MORF4L1 NM_006791.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.84
• Publications: 0 publications found

Genes affected

MORF4L1 (HGNC:16989): (mortality factor 4 like 1) Enables protein N-terminus binding activity. Involved in double-strand break repair via homologous recombination and histone modification. Located in nuclear speck. Part of NuA4 histone acetyltransferase complex and Sin3 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13744184).
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006791.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORF4L1	NM_006791.4	MANE Select	c.103A>G	p.Ile35Val	missense	Exon 3 of 12	NP_006782.1	Q9UBU8-2
	MORF4L1	NM_206839.3		c.103A>G	p.Ile35Val	missense	Exon 3 of 13	NP_996670.1	Q9UBU8-1
	MORF4L1	NM_001265604.2		c.-162A>G		5_prime_UTR	Exon 3 of 12	NP_001252533.1	Q9UBU8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORF4L1	ENST00000426013.7	TSL:1 MANE Select	c.103A>G	p.Ile35Val	missense	Exon 3 of 12	ENSP00000408880.2	Q9UBU8-2
	MORF4L1	ENST00000331268.9	TSL:1	c.103A>G	p.Ile35Val	missense	Exon 3 of 13	ENSP00000331310.5	Q9UBU8-1
	MORF4L1	ENST00000558893.5	TSL:1	n.148A>G		non_coding_transcript_exon	Exon 3 of 7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000124 AC: 3 AN: 242486 AF XY: 0.00000763

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000932

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000759 AC: 11 AN: 1450036 Hom.: 0 Cov.: 29 AF XY: 0.0000111 AC XY: 8 AN XY: 721338

African (AFR) AF: 0.00 AC: 0 AN: 32912

American (AMR) AF: 0.0000945 AC: 4 AN: 42320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25988

East Asian (EAS) AF: 0.00 AC: 0 AN: 39438

South Asian (SAS) AF: 0.00 AC: 0 AN: 83456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5528

European-Non Finnish (NFE) AF: 0.00000542 AC: 6 AN: 1107080

Other (OTH) AF: 0.0000167 AC: 1 AN: 59960

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.039
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.47	N
PhyloP100		4.8
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.14
Sift	Benign	0.73	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.39		Gain of methylation at K36 (P = 0.103)
MVP		0.36
MPC		0.43
ClinPred		0.16	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.12
Mutation Taster		=238/62	polymorphism

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

Other links and lift over

dbSNP: rs753870808; hg19: chr15-79172869;