chr14-21380742-T-A

Variant names:

• chr14-21380742-T-A
• rs9322978
• NM_007192.4:c.66+3120A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007192.4(SUPT16H):​c.66+3120A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 151,908 control chromosomes in the GnomAD database, including 51,664 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.82 (51664 hom., cov: 29)
• Consequence: SUPT16H NM_007192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.16
• Publications: 2 publications found

Genes affected

SUPT16H (HGNC:11465): (SPT16 homolog, facilitates chromatin remodeling subunit) Transcription of protein-coding genes can be reconstituted on naked DNA with only the general transcription factors and RNA polymerase II. However, this minimal system cannot transcribe DNA packaged into chromatin, indicating that accessory factors may facilitate access to DNA. One such factor, FACT (facilitates chromatin transcription), interacts specifically with histones H2A/H2B to effect nucleosome disassembly and transcription elongation. FACT is composed of an 80 kDa subunit and a 140 kDa subunit; this gene encodes the 140 kDa subunit. [provided by RefSeq, Feb 2009]

SUPT16H Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with dysmorphic facies and thin corpus callosum

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUPT16H	NM_007192.4	c.66+3120A>T		intron_variant	Intron 1 of 25	ENST00000216297.7	NP_009123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUPT16H	ENST00000216297.7	c.66+3120A>T		intron_variant	Intron 1 of 25	1	NM_007192.4	ENSP00000216297.2

Frequencies

GnomAD3 genomes AF: 0.816 AC: 123820 AN: 151790 Hom.: 51662 Cov.: 29

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.912

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.863

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.815 AC: 123861 AN: 151908 Hom.: 51664 Cov.: 29 AF XY: 0.814 AC XY: 60463 AN XY: 74262

African (AFR) AF: 0.623 AC: 25763 AN: 41362

American (AMR) AF: 0.805 AC: 12268 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 3231 AN: 3470

East Asian (EAS) AF: 0.878 AC: 4535 AN: 5168

South Asian (SAS) AF: 0.911 AC: 4384 AN: 4812

European-Finnish (FIN) AF: 0.855 AC: 9026 AN: 10560

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.907 AC: 61699 AN: 67990

Other (OTH) AF: 0.864 AC: 1818 AN: 2104

Alfa AF: 0.845 Hom.: 6440

Bravo AF: 0.802

Asia WGS AF: 0.872 AC: 3031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.0030
DANN	Benign	0.80
PhyloP100		-4.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs9322978; hg19: chr14-21848901;