10-73232856-T-G

Variant names:

• chr10-73232856-T-G
• rs2292948
• NM_173348.2:c.1128-83T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173348.2(FAM149B1):​c.1128-83T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 666,996 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: FAM149B1 NM_173348.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• Publications: 0 publications found

Genes affected

FAM149B1 (HGNC:29162): (family with sequence similarity 149 member B1) Involved in cilium assembly and protein localization to cilium. Predicted to be located in cilium. Implicated in Joubert syndrome. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC9 (HGNC:19123): (DnaJ heat shock protein family (Hsp40) member C9) Enables chaperone binding activity; heat shock protein binding activity; and histone binding activity. Involved in nucleosome assembly and positive regulation of ATPase activity. Located in several cellular components, including cytosol; extracellular space; and nucleoplasm. Part of chaperone complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000310418 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173348.2. 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
	FAM149B1	NM_173348.2	MANE Select	c.1128-83T>G		intron	N/A	NP_775483.1	Q96BN6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM149B1	ENST00000242505.11	TSL:5 MANE Select	c.1128-83T>G		intron	N/A	ENSP00000242505.6	Q96BN6-1
	FAM149B1	ENST00000372955.7	TSL:1	c.924-83T>G		intron	N/A	ENSP00000362046.3	H7BY93
	FAM149B1	ENST00000959965.1		c.1122-83T>G		intron	N/A	ENSP00000630024.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000150 AC: 1 AN: 666996 Hom.: 0 AF XY: 0.00000285 AC XY: 1 AN XY: 350340

African (AFR) AF: 0.00 AC: 0 AN: 17114

American (AMR) AF: 0.00 AC: 0 AN: 31216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19412

East Asian (EAS) AF: 0.00 AC: 0 AN: 32294

South Asian (SAS) AF: 0.00 AC: 0 AN: 61012

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3104

European-Non Finnish (NFE) AF: 0.00000235 AC: 1 AN: 424834

Other (OTH) AF: 0.00 AC: 0 AN: 33786

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.8
DANN	Benign	0.61
PhyloP100		-0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2292948; hg19: chr10-74992614;